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Abstract Background Understanding evolutionary processes that drive genome reduction requires determining the tempo (rate) and the mode (size and types of deletions) of gene losses. In this study, we analysed five endosymbiotic genome sequences of the gamma-proteobacteria (three different Buchnera aphidicola strains, Wigglesworthia glossinidia, Blochmannia floridanus) to test if gene loss could be driven by the selective importance of genes. We used a parsimony method to reconstruct a minimal ancestral genome of insect endosymbionts and quantified gene loss along the branches of the phylogenetic tree. To evaluate the selective or functional importance of genes, we used a parameter that measures the level of adaptive codon bias in E. coli (i.e. codon adaptive index, or CAI), and also estimates of evolutionary rates (Ka) between pairs of orthologs either in free-living bacteria or in pairs of symbionts. Results Our results demonstrate that genes lost in the early stages of symbiosis were on average less selectively constrained than genes conserved in any of the extant symbiotic strains studied. These results also extend to more recent events of gene losses (i.e. among Buchnera strains) that still tend to concentrate on genes with low adaptive bias in E. coli and high evolutionary rates both in free-living and in symbiotic lineages. In addition, we analyzed the physical organization of gene losses for early steps of symbiosis acquisition under the hypothesis of a common origin of different symbioses. In contrast with previous findings we show that gene losses mostly occurred through loss of rather small blocks and mostly in syntenic regions between at least one of the symbionts and present-day E. coli. Conclusion At both ancient and recent stages of symbiosis evolution, gene loss was at least partially influenced by selection, highly conserved genes being retained more readily than lowly conserved genes: although losses might result from drift due to the bottlenecking of endosymbiontic populations, we demonstrated that purifying selection also acted by retaining genes of greater selective importance.

The standardisation of protocols and discussion of therapeutic procedures in the rehabilitation of turtles affected by oil spills are necessary to optimise the recovery time and increase the chances of survival of these animals. This study aimed at reporting the processes adopted for the stabilisation, decontamination, rehabilitation and release of an oiled olive ridley sea turtle (Lepidochelys olivacea), rescued alive on September 23, 2019, at Santa Rita Beach, Extremoz municipality, Rio Grande do Norte, Brazil. Its entire body was covered by oil. At first, the animal was mechanically dry cleaned using a gauze soaked in mineral oil in the keratinised regions (carapace and plastron) and a gauze soaked in vegetable oil was used on the oral, nasal, ocular, and cloacal mucous membranes. The second stage of the oil removal consisted of washing the animal with heated pressurised water (39 °C) and a neutral detergent using a soft foam sponge. The animal received treatment with antitoxins, antibiotics, analgesics, gastrointestinal protectors, and fluid therapy. After 7 days of treatment, the blood count showed that all the parameters were within the normal range. The oil cleaning process and the therapeutic protocol used in the rehabilitation of the olive ridley sea turtle were efficient.

Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of nuclear peroxisome proliferator-activated receptor alpha (PPARα) to exert their biological functions, which include the regulation of appetite and metabolism. Increasing evidence also suggests that OEA may participate in the control of reward-related behaviours. However, direct experimental evidence for the role of the OEA-PPARα receptor interaction in drug-mediated behaviours, such as cocaine-induced behavioural phenotypes, is lacking. The present study explored the role of OEA and its receptor PPARα on the psychomotor and rewarding responsiveness to cocaine using behavioural tests indicative of core components of addiction. We found that acute administration of OEA (1, 5 or 20 mg/kg, i.p.) reduced spontaneous locomotor activity and attenuated psychomotor activation induced by cocaine (20 mg/kg) in C57Bl/6 mice. However, PPARα receptor knockout mice showed normal sensitization, although OEA was capable of reducing behavioural sensitization with fewer efficacies. Furthermore, conditioned place preference and reinstatement to cocaine were intact in these mice. Our results indicate that PPARα receptor does not play a critical, if any, role in mediating short- and long-term psychomotor and rewarding responsiveness to cocaine. However, further research is needed for the identification of the targets of OEA for its inhibitory action on cocaine-mediated responses. [ABSTRACT FROM AUTHOR]

Background and Purpose: Peripheral blockade of cannabinoid CB(1) receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects of centrally acting CB(1) receptor antagonists. In this study we analysed the effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist with poor brain penetration, in an animal model of diet-induced obesity.Experimental Approach: To induce obesity, male Wistar rats were fed a high-fat diet (HFD; 60 kcal% fat) whereas controls received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding, animals received a daily i.p. injection of vehicle or 3 mg·kg(-1) LH-21 for 10 days. Plasma and liver samples were used for biochemical analyses whereas visceral fat-pad samples were analysed for lipid metabolism gene expression using real-time RT-PCR. In addition, the potential of LH-21 to interact with hepatic cytochrome P450 isoforms and cardiac human Ether-à-go-go Related Gene (hERG) channels was evaluated.Key Results: LH-21 reduced feeding and body weight gain in HFD-fed animals compared with the control group fed SD. In adipose tissue, this effect was associated with decreased gene expression of: (i) leptin; (ii) lipogenic enzymes, including SCD-1; (iii) CB(1) receptors; and (iv) both PPARα and PPARγ. Although there were no significant differences in plasma parameters between HFD- and SD-fed rats, LH-21 did not seem to induce hepatic, cardiac or renal toxicity.Conclusions and Implications: These results support the hypothesis that treatment with the peripherally neutral acting CB(1) receptor antagonist, LH-21, may promote weight loss through modulation of visceral adipose tissue. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Insulitis, a hallmark of inflammation preceding autoimmune type 1 diabetes, leads to the eventual loss of functional beta cells. However, functional beta cells can persist even in the face of continuous insulitis. Despite advances in immunosuppressive treatments, maintaining functional beta cells to prevent insulitis progression and hyperglycaemia remains a challenge. The cannabinoid type 1 receptor (CB1R), present in immune cells and beta cells, regulates inflammation and beta cell function. Here, we pioneer an ex vivo model mirroring human insulitis to investigate the role of CB1R in this process., Methods: CD4 + T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) from male and female individuals at the onset of type 1 diabetes and from non-diabetic individuals, RNA was extracted and mRNA expression was analysed by real-time PCR. Single beta cell expression from donors with type 1 diabetes was obtained from data mining. Patient-derived human islets from male and female cadaveric donors were 3D-cultured in solubilised extracellular matrix gel in co-culture with the same donor PBMCs, and incubated with cytokines (IL-1β, TNF-α, IFN-γ) for 24-48 h in the presence of vehicle or increasing concentrations of the CB1R blocker JD-5037. Expression of CNR1 (encoding for CB1R) was ablated using CRISPR/Cas9 technology. Viability, intracellular stress and signalling were assayed by live-cell probing and real-time PCR. The islet function measured as glucose-stimulated insulin secretion was determined in a perifusion system. Infiltration of immune cells into the islets was monitored by microscopy. Non-obese diabetic mice aged 7 weeks were treated for 1 week with JD-5037, then euthanised. Profiling of immune cells infiltrated in the islets was performed by flow cytometry., Results: CNR1 expression was upregulated in circulating CD4 + T cells from individuals at type 1 diabetes onset (6.9-fold higher vs healthy individuals) and in sorted islet beta cells from donors with type 1 diabetes (3.6-fold higher vs healthy counterparts). The peripherally restricted CB1R inverse agonist JD-5037 arrested the initiation of insulitis in humans and mice. Mechanistically, CB1R blockade prevented islet NO production and ameliorated the ATF6 arm of the unfolded protein response. Consequently, cyto/chemokine expression decreased in human islets, leading to sustained islet cell viability and function., Conclusions/interpretation: These results suggest that CB1R could be an interesting target for type 1 diabetes while highlighting the regulatory mechanisms of insulitis. Moreover, these findings may apply to type 2 diabetes where islet inflammation is also a pathophysiological factor., Data Availability: Transcriptomic analysis of sorted human beta cells are from Gene Expression Omnibus database, accession no. GSE121863, available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM3448161 ., (© 2024. The Author(s).)

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD., Competing Interests: Declaration of competing interest Christos S. Mantzoros has recused himself as EIC from handling this manuscript, reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. Christopher D Byrne has received an independent research grant from Echosens. France. W. Kim received honoraria for lectures from GSK, Hanmi, KOBIOLABS, and Novo Nordisk; consulting fees from Boehringer-Ingelheim, GSK, Novo Nordisk, Ildong, YUHAN, Hanmi, HK Inoen, Standigm, PharmaKing, Olix Pharma, TSD Life Sciences, Daewoong, QUEST, Therasid Bioscience, and Korea United Pharm; grants from GSK, Gilead, Novartis, Pfizer, Roche, Springbank, Ildong, BMS, DaeWoong, Hanmi, Novo Nordisk, Galmed, Enyo, and KOBIOLABS; stock options from KOBIOLABS and Lepidyne; and founded Remedygen outside the submitted work. Anoop Misra has received honorarium for lectures from Astra Zendeca, Boehringer Ingelgheim, Janssen, Lupin, Novo Nordisk and US Vitamins. Yusuf Yilmaz has served as a consultant or advisory board member for Zydus and Novo Nordisk. Boehringer Ingelheim. Wah Kheong Chan has served as a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Ming-Lung Yu has received research support (grant) from Abbvie, BMS, Gilead, Merck and Roche diagnostics, served as a consultant of Abbott, Abbvie, BMS, Gilead, Roche and Roche diagnostics, and speaker of Abbvie, BMS, Eisai, Gilead, Roche and Roche diagnostics. Vincent Wong has served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, Novo Nordisk, and Unilab. He has received a research grant from Gilead Sciences, and is a co-founder of Illuminatio Medical Technology. Giada Sebastiani has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead, and has received unrestricted research funding from Theratecnologies Inc. Jacob George has served on advisory Boards and receives honoraria for talks from Novo Nordisk, Astra Zeneca, Roche, BMS, Pfizer, Cincera, Pharmaxis, Boehringer Mannheim, CSL, Gilead, Eisai. Carolyn Newberry serves as a consultant for Nestle Nutrition Sciences. The other authors declare no conflict of interest related to the preparation of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts., (© 2024. The Author(s).)

We explored the metabolic integration of Blattella germanica and its obligate endosymbiont Blattabacterium cuenoti by the transcriptomic analysis of the fat body of quasi-aposymbiotic cockroaches, where the endosymbionts were almost entirely removed with rifampicin. Fat bodies from quasi-aposymbiotic insects displayed large differences in gene expression compared to controls. In quasi-aposymbionts, the metabolism of phenylalanine and tyrosine involved in cuticle sclerotization and pigmentation increased drastically to compensate for the deficiency in the biosynthesis of these amino acids by the endosymbionts. On the other hand, the uricolytic pathway and the biosynthesis of uric acid were severely decreased, probably because the reduced population of endosymbionts was unable to metabolize urea to ammonia. Metabolite transporters that could be involved in the endosymbiosis process were identified. Immune system and antimicrobial peptide (AMP) gene expression was also reduced in quasi-aposymbionts, genes encoding peptidoglycan-recognition proteins, which may provide clues for the maintenance of the symbiotic relationship, as well as three AMP genes whose involvement in the symbiotic relationship will require additional analysis. Finally, a search for AMP-like factors that could be involved in controlling the endosymbiont identified two orphan genes encoding proteins smaller than 200 amino acids underexpressed in quasi-aposymbionts, suggesting a role in the host-endosymbiont relationship.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Despite the abundance of registered clinical trials worldwide, the availability of effective drugs for obesity treatment is limited due to their associated side effects. Thus, there is growing interest in therapies that stimulate energy expenditure in white adipose tissue. Recently, we demonstrated that the delivery of a miR-21 mimic using JetPEI effectively inhibits weight gain in an obese mouse model by promoting metabolism, browning, and thermogenesis, suggesting the potential of miR-21 mimic as a treatment for obesity. Despite these promising results, the implementation of more advanced delivery system techniques for miR-21 mimic would greatly enhance the advancement of safe and efficient treatment approaches for individuals with obesity in the future. Our objective is to explore whether a new delivery system based on gold nanoparticles and Gemini surfactants (Au@16-ph-16) can replicate the favorable effects of the miR-21 mimic on weight gain, browning, and thermogenesis. We found that dosages as low as 0.2 μg miR-21 mimic /animal significantly inhibited weight gain and induced browning and thermogenic parameters. This was evidenced by the upregulation of specific genes and proteins associated with these processes, as well as the biogenesis of beige adipocytes and mitochondria. Significant increases in miR-21 levels were observed in adipose tissue but not in other tissue types. Our data indicates that Au@16-ph-16 could serve as an effective delivery system for miRNA mimics, suggesting its potential suitability for the development of future clinical treatments against obesity., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Guiana dolphins, Sotalia guianensis, are vulnerable to extinction along their distribution on the Brazilian coast and assessing chemical pollution is of utmost importance for their conservation. For this study, 51 carcasses of Guiana dolphins were sampled across the Brazilian coast to investigate legacy and emerging brominated flame retardants (BFRs) as well as the naturally-produced MeO-BDEs. PBDEs and MeO-BDEs were detected in all samples analyzed, whereas emerging BFRs were detected in 16 % of the samples, all in Rio de Janeiro state. PBDE concentrations varied between 2.24 and 799 ng.g -1 lipid weight (lw), emerging BFRs between 0.12 and 1.51 ng.g -1 lw and MeO-BDEs between 3.82 and 10,247 ng.g -1 lw. Concentrations of legacy and emerging BFRs and natural compounds varied considerably according to the sampling site and reflected both the local anthropogenic impact of the region and the diversity/mass of biosynthesizers. The PBDE concentrations are lower than what was found for delphinids in the Northern Hemisphere around the same sampling period and most sampling sites presented mean concentrations lower than the limits for endocrine disruption known to date for marine mammals of 460 ng.g -1 lw, except for sampled from Santa Catarina state, in Southern Brazil. Conversely, MeO-BDE concentrations are higher than those of the Northern Hemisphere, particularly close to the Abrolhos Bans and Royal Charlotte formation, that are hotspots for biodiversity. Despite the elevated concentrations reported for this group, there is not much information regarding the effects of such elevated concentrations for these marine mammals. The distinct patterns observed along the Brazilian coast show that organobrominated compounds can be used to identify the ecological segregation of delphinids and that conservation actions should be planned considering the local threats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The progression of obesity and type 2 diabetes (T2D) is intricately linked with adipose tissue (AT) angiogenesis. Despite an established network of microRNAs (miRNAs) regulating AT function, the specific role of angiogenic miRNAs remains less understood. The miR-221/222 cluster has recently emerged as being associated with antiangiogenic activity. However, no studies have explored its role in human AT amidst the concurrent development of obesity and T2D. Therefore, this study aims to investigate the association between the miR-221-3p/222-3p cluster in human AT and its regulatory network with obesity and T2D. MiR-221-3p/222-3p and their target gene (TG) expression levels were quantified through qPCR in visceral (VAT) and subcutaneous (SAT) AT from patients ( n = 33) categorized based on BMI as normoweight (NW) and obese (OB) and by glycemic status as normoglycemic (NG) and type 2 diabetic (T2D) subjects. In silico analyses of miR-221-3p/222-3p and their TGs were conducted to identify pertinent signaling pathways. The results of a multivariate analysis, considering the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, revealed statistically significant distinctions when accounting for variables such as tissue depot, obesity, sex, and T2D as independent factors. Furthermore, both miRNAs and their TGs exhibited differential expression patterns based on obesity severity, glycemic status, sex, and type of AT depot. Our in silico analysis indicated that miR-221-3p/222-3p cluster TGs predominantly participate in angiogenesis, WNT signaling, and apoptosis pathways. In conclusion, these findings underscore a promising avenue for future research, emphasizing the miR-221-3p/222-3p cluster and its associated regulatory networks as potential targets for addressing obesity and related metabolic disorders.

This article reviews the legal frameworks of diminished criminal responsibility in eighteen civil law jurisdictions across the globe-Brazil, Chile, China, the Czech Republic, Finland, France, Germany, Greece, Italy, Japan, Luxembourg, Poland, Portugal, Russia, Spain, Switzerland, Taiwan, and Turkey. Specifically, it reports the legal standards and main features of partial responsibility, associated penalty reductions, and potential dispositions following a partial responsibility finding. It also surveys empirical data on the prevalence of diminished responsibility as compared to criminal nonresponsibility. This article, which reflects contemporary penal codes and draws from both English and non-English sources, is the only known existing source to compile these partial responsibility standards or to delineate their precise sentencing consequences. It is also the only known source in English to describe Portugal's and Chile's treatment of diminished responsibility. Providing a comparative overview of graduated responsibility in nearly twenty countries invites global discussion on whether and how society should recognize partial responsibility, as well as the punitive and therapeutic consequences that should attend this finding., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Characterized by high levels of emotional exhaustion and depersonalization and reduced professional accomplishment, burnout syndrome has been a major cause of psychic illness in nursing workers, with a serious impact on the quality of services and on patient safety., Objectives: To analyze the correlation between organizational climate, job satisfaction, and burnout in nursing workers., Methods: This is a cross-sectional study with a sample of 534 Brazilian nursing workers. We used the Organizational Climate Scale for Health Organizations, the Job Satisfaction Questionnaire (S20/23), and the Maslach Burnout Inventory. An analytical descriptive analysis of the data was performed using relative and absolute frequencies, mean, standard deviation, minimum, maximum, and correlation test between the variables., Results: Organizational climate and job satisfaction were evaluated as regular. With regard to burnout, moderate levels of emotional exhaustion, low levels of depersonalization, and high levels of professional accomplishment were observed. A strong positive correlation was found between job satisfaction and organizational climate; in addition to a moderate negative correlation between emotional exhaustion and both organizational climate and job satisfaction, and a moderate negative correlation between depersonalization and job satisfaction., Conclusions: Organizational climate and job satisfaction had a negative correlation with burnout dimensions, representing possible protective factors., Competing Interests: Conflicts of interest: None

Studies on novel methodologies addressed to quantification of anthropogenic marine debris (AMD) types ingested by green turtles (Chelonia mydas) is not common in the scientific literature. To fill this gap, we used the alimentary index (IAi) to quantify and classify AMD ingested by green turtles stranded in the Potiguar Basin, northeastern Brazil. We classified 295 green turtles as juveniles (JUV-I (n = 190) and JUV-II (n = 58)) and adults (ADU (n = 47)). We collected gut contents during necropsy and analyzed them using the IAi. The IAi values were categorized as main (IAi ≥ 0.5), secondary (0.25 ≤ IAi < 0.5), and accessory (IAi < 0.25). The results revealed that transparent soft plastic was an accessory item for the three size groups and the second most frequent item (IAi = 0.23) for JUV-I. Our study brings insights into the application of the IAi to evaluate the amount and types of AMD ingested by green turtles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human studies have examined the health benefits of olive oils rich in these biophenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity., Methods: Randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m 2 ) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No changes in diet or physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, glucose handling and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis., Results: A total of 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P = 0.041). Total antioxidant status increased and lipid and organic peroxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P < 0.05). Decreases in weight, BMI and blood glucose (p < 0.05) were found after treatment with EVOO and not with OO., Conclusions: Treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare for this study. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. Cortijo Suerte Alta S.L. (Albendín, Baena, Córdoba, Spain) and Jacoliva S.L. (Pozuelo de Zarzón, Cáceres, Spain) supplied for free the olive oils but had no role in the analysis and interpretation of the data as well as in the decision to publish the findings., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sea turtles are affected by pollutants worldwide, and the polycyclic aromatic hydrocarbons (PAHs) have been detected in different types of samples and at high levels in some cases. The present study brings concentrations of 37 PAHs in liver samples of 17 green turtles Chelonia mydas stranded in northeastern Brazil [four with cutaneous tumors of fibropapillomatosis (FP), being classified as FP+]. Six PAHs were detected in 100% of the liver samples, and all alkylated PAHs were frequently quantified. High levels of phenanthrene (771.20 and 794.43 ng g -1 d.w.) and fluorene (1882.36 ng g -1 d.w.) were found in three females FP- (without FP cutaneous tumors). On the other hand, one green turtle FP+ had the higher level of naphthalene (531.70 ng g -1 d.w.), compound detected in 82.35 % of the samples. Our study brings additional baseline of organic pollutants in green turtles, improving knowledge on bioaccumulation of these compounds in sea turtles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions of the head and neck, mainly the salivary glands. In general, the primary treatment modality for ACC is surgical resection and, in some cases, postoperative radiotherapy. However, no effective systemic treatment is available for patients with advanced disease. Furthermore, this tumor type is characterized by recurrent molecular alterations, especially rearrangements involving the MYB, MYBL1 , and NFIB genes. In addition, they also reported copy number alterations (CNAs) that impact genes. One of them is C-KIT , mutations that affect signaling pathways such as NOTCH, PI3KCA, and PTEN, as well as alterations in chromatin remodeling genes. The identification of new molecular targets enables the development of specific therapies. Despite ongoing investigations into immunotherapy, tyrosine kinase inhibitors, and anti-angiogenics, no systemic therapy is approved by the FDA for ACC. In this review, we report the genetic and cytogenetic findings on head and neck ACC, highlighting possible targets for therapeutic interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 da Silva, Carvalho de Azevedo, Ralph, Pinheiro, Freitas and Calcagno.)

Objective: The increasing significance of medicolegal evaluation following maxillofacial traumatic events constitutes a complex issue. This clinical research aimed to assess the current etiology of oral and maxillofacial injuries in Portuguese population., Material and Methods: An epidemiological clinical observational study was conducted in Centro Hospitalar Lisboa Norte on a sample of 384 subjects diagnosed with oral and maxillofacial trauma, between 2018 and 2020. Data were collected through clinical reports and analyzed using SPSS version 27., Results: Women and men were nearly identical in the number and distribution, with 49.5% females and 50.5% males. In 2020, there was a decrease in the number of traumatic incidents compared to other years. Falls or accidental descents were found to be the most common cause of injury, accounting for 44.3%, followed by assaults accounting for 24.7%. A total of 84 subjects exhibited soft tissue injuries related to periodontal region. The upper central incisors (174) were the most frequently affected teeth with uncomplicated fractures, and the predominant form of treatment was the administration of pain medication., Conclusion: A correlation between falls or accidental descents, female subjects, and advancing age, as well as between assaults, male subjects, and adults, has been established. Falls or accidental descents and assault were the predominant etiologies, and the year 2020 exhibited a decrease in the incidents of traumatic events., Competing Interests: Conflict of Interest: The authors declare no competing interests.

Aims: To compare efficacy and safety of degludec 100 IU/mL (Deg-100) and glargine 300 IU/mL (Gla-300) in adults with type 1 diabetes., Methods: Open-label, single-center, randomized, parallel-group, 24-week trial in adults with type 1 diabetes, on basal-bolus insulin therapy, HbA1c ≤ 10%, using self-monitoring blood glucose. Participants were randomized 1:1 to a basal-bolus insulin regimen with Deg-100 (N = 129) or Gla-300 (N = 131). Primary efficacy endpoint: mean change in HbA1c from baseline to week-24. Main safety outcome: incidence rate of hypoglycemia during the study. Quality of life (DQOL) and satisfaction with diabetes treatment (DTSQ) were assessed., Results: At week 24, after adjusting for baseline HbA1c, the decrease in HbA1c did not differ between groups: Deg-100 (-0.07 ± 0.7%) and Gla-300 (-0.16 ± 0.77%) (P = 0.320). There were no significant differences between groups in HbA1c, nocturnal hypoglycemia, severe hypoglycemia, DQOL, or DTSQ scores. The incidence rates of hypoglycemia < 3.9 mmol/L (Deg-100: 115.24 events/person-year vs Gla-300: 99.01 events/person-year, p < 0.001); and < 3.0 mmol/L (Deg-100: 41.17 events/person-year vs Gla-300: 34.29 events/person-year, p < 0.001) were different between groups., Conclusions: Deg-100 and Gla-300 have similar metabolic efficacy, incidence ratio of nocturnal and severe hypoglycemia, DQOL and DTSQ scores. Differences in the incidence rate of hypoglycemia < 3.9 mmol/L and < 3.0 mmol/L should be confirmed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Antimicrobial peptide (AMP) genes, triggered by Toll and IMD pathways, are essential components of the innate immune system in the German cockroach Blattella germanica . Besides their role in killing pathogenic bacteria, AMPs could be involved in controlling its symbiotic systems (endosymbiont and microbiota). We found that the IMD pathway was active in the adult female transcriptomes of six tissues (salivary glands, foregut, midgut, hindgut, Malpighian tubules and fat body) and hemolymph. Total expression of AMP genes was high in hemolymph and salivary glands and much lower in the other sample types. The expression of specific AMP genes was very heterogeneous among sample types. Two genes, defensin&#95;g10 and drosomycin&#95;g5 , displayed relevant expression in the seven sample types, although higher in hemolymph. Other genes only displayed high expression in one tissue. Almost no expression of attacin-like and blattellicin genes was observed in any sample type, although some of them were among the genes with the highest expression in adult female whole bodies. The expression of AMP genes in salivary glands could help control pathogens ingested with food and even determine gut microbiota composition. The low expression levels in midgut and hindgut are probably related to the presence of beneficial microbiota. Furthermore, a reduction in the expression of AMP genes in fat body could be the way to prevent damage to the population of the endosymbiont Blattabacterium cuenoti within bacteriocytes.

Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis . We report construction and analyses of the complete genome sequence of M. lepromatosis FJ924. The genome contained 3,271,694 nucleotides to encode 1,789 functional genes and 1,564 pseudogenes. It shared 1,420 genes and 885 pseudogenes (71.4%) with M. leprae but differed in 1,281 genes and pseudogenes (28.6%). In phylogeny, the leprosy bacilli started from a most recent common ancestor (MRCA) that diverged ~30 million years ago (Mya) from environmental organism Mycobacterium haemophilum. The MRCA then underwent reductive evolution with pseudogenization, gene loss, and chromosomal rearrangements. Analysis of the shared pseudogenes estimated the pseudogenization event ~14 Mya, shortly before species bifurcation. Afterwards, genomic changes occurred to lesser extent in each species. Like M. leprae, four major types of highly repetitive sequences were detected in M. lepromatosis , contributing to chromosomal rearrangements within and after MRCA. Variations in genes and copy numbers were noted, such as three copies of the gene encoding bifunctional diguanylate cyclase/phosphodiesterase in M. lepromatosis , but single copy in M. leprae; 6 genes encoding the TetR family transcriptional regulators in M. lepromatosis , but 11 such genes in M. leprae; presence of hemW gene in M. lepromatosis , but absence in M. leprae; and others. These variations likely aid unique pathogenesis, such as diffuse lepromatous leprosy associated with M. lepromatosis , while the shared genomic features should explain the common pathogenesis of dermatitis and neuritis in leprosy. Together, these findings and the genomic data of M. lepromatosis may facilitate future research and care for leprosy. IMPORTANCE Leprosy is a dreaded infection that still affects millions of people worldwide. Mycobacterium lepromatosis is a recently recognized cause in addition to the well-known Mycobacterium leprae. M. lepromatosis is likely specific for diffuse lepromatous leprosy, a severe form of the infection and endemic in Mexico. This study constructed and annotated the complete genome sequence of M. lepromatosis FJ924 and performed comparative genomic analyses with related mycobacteria. The results afford new and refined insights into the genome size, gene repertoire, pseudogenes, phylogenomic relationship, genome organization and plasticity, process and timing of reductive evolution, and genetic and proteomic basis for pathogenesis. The availability of the complete M. lepromatosis genome may prove to be useful for future research and care for the infection.

LRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE 2 levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist-ONO-8130-negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE 2 /PTGER1 signaling axis as a key pathway mediating BL001 survival properties., Competing Interests: Two patents (WO, 2011 144725 A2 and WO, 2016 156531 A1) related to BL001 have been published of which B.R.G. and N.C.V. are inventors. These patents have been licensed to ARIDDAD Therapeutics, a Biotech spinoff cofounded by B.R.G. and N.C.V. along with European business partners. The other authors declare no competing interests., (© 2022 The Author(s).)

Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.

Several studies have proved that glial cells, as well as neurons, play a role in pain pathophysiology. Most of these studies have focused on the contribution of central glial cells (e.g., microglia and astrocytes) to neuropathic pain. Likewise, some works have suggested that peripheral glial cells, particularly satellite glial cells (SGCs), and the crosstalk between these cells and the sensory neurons located in the peripheral ganglia, play a role in the phenomenon that leads to pain. Nonetheless, the study of SGCs may be challenging, as the validity of studying those cells in vitro is still controversial. In this study, a research protocol was developed to examine the potential use of primary mixed neuronal-glia cell cultures obtained from the trigeminal ganglion cells (TGCs) of neonate mice (P10-P12). Primary cultures were established and analyzed at 4 h, 24 h, and 48 h. To this purpose, phase contrast microscopy, immunocytochemistry with antibodies against anti-βIII-tubulin and Sk3, scanning electron microscopy, and time-lapse photography were used. The results indicated the presence of morphological changes in the cultured SGCs obtained from the TGCs. The SGCs exhibited a close relationship with neurons. They presented a round shape in the first 4 h, and a more fusiform shape at 24 h and 48 h of culture. On the other hand, neurons changed from a round shape to a more ramified shape from 4 h to 48 h. Intriguingly, the expression of SK3, a marker of the SGCs, was high in all samples at 4 h, with some cells double-staining for SK3 and βIII-tubulin. The expression of SK3 decreased at 24 h and increased again at 48 h in vitro. These results confirm the high plasticity that the SGCs may acquire in vitro. In this scenario, the authors hypothesize that, at 4 h, a group of the analyzed cells remained undifferentiated and, therefore, were double-stained for SK3 and βIII-tubulin. After 24 h, these cells started to differentiate into SCGs, which was clearer at 48 h in the culture. Mixed neuronal-glial TGC cultures might be implemented as a platform to study the plasticity and crosstalk between primary sensory neurons and SGCs, as well as its implications in the development of chronic orofacial pain.

The atypical cannabinoid Abn-CBD improves the inflammatory status in preclinical models of several pathologies, including autoimmune diseases. However, its potential for modulating inflammation in autoimmune type 1 diabetes (T1D) is unknown. Herein we investigate whether Abn-CBD can modulate the inflammatory response during T1D onset using a mouse model of T1D (non-obese diabetic- (NOD)-mice) and of beta cell damage (streptozotocin (STZ)-injected mice). Six-week-old female NOD mice were treated with Abn-CBD (0.1-1 mg/kg) or vehicle during 12 weeks and then euthanized. Eight-to-ten-week-old male C57Bl6/J mice were pre-treated with Abn-CBD (1 mg/kg of body weight) or vehicle for 1 week, following STZ challenge, and euthanized 1 week later. Blood, pancreas, pancreatic lymph nodes (PLNs) and T cells were collected and processed for analysis. Glycemia was also monitored. In NOD mice, treatment with Abn-CBD significantly reduced the severity of insulitis and reduced the pro-inflammatory profile of CD4 + T cells compared to vehicle. Concomitantly, Abn-CBD significantly reduced islet cell apoptosis and improved glucose tolerance. In STZ-injected mice, Abn-CBD decreased circulating proinflammatory cytokines and ameliorated islet inflammation reducing intra-islet phospho-NF-κB and TXNIP. Abn-CBD significantly reduced 2 folds intra-islet CD8 + T cells and reduced Th1/non-Th1 ratio in PLNs of STZ-injected mice. Islet cell apoptosis and intra-islet fibrosis were also significantly reduced in Abn-CBD pre-treated mice compared to vehicle. Altogether, Abn-CBD reduces circulating and intra-islet inflammation, preserving islets, thus delaying the progression of insulitis. Hence, Abn-CBD and related compounds emerge as new candidates to develop pharmacological strategies to treat the early stages of T1D., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Blattella germanica presents a very complex symbiotic system, involving the following two kinds of symbionts: the endosymbiont Blattabacterium and the gut microbiota. Although the role of the endosymbiont has been fully elucidated, the function of the gut microbiota remains unclear. The study of the gut microbiota will benefit from the availability of insects deprived of Blattabacterium. Our goal is to determine the effect of the removal (or, at least, the reduction) of the endosymbiont population on the cockroach's fitness, in a normal gut microbiota community. For this purpose, we treated our cockroach population, over several generations, with rifampicin, an antibiotic that only affects the endosymbiont during its extracellular phase, and decreases its amount in the following generation. As rifampicin also affects gut bacteria that are sensitive to this antibiotic, the treatment was performed during the first 12 days of the adult stage, which is the period when the endosymbiont infects the oocytes and lacks bacteriocyte protection. We found that after this antibiotic treatment, the endosymbiont population remained extremely reduced and only the microbiota was able to recover, although it could not compensate for the endosymbiont role, and the host's fitness was drastically affected. This accomplished reduction, however, is not homogenous and requires further study to develop stable quasi-aposymbiotic cockroaches.

MicroRNAs (miRNAs) are promising drug targets for obesity and metabolic disorders. Recently, miRNA mimics are providing a unique mechanism of action that guides the process for drug development and sets out the context of their therapeutic application. miRNA (miR)-21 expression in white adipose tissue (WAT) has been associated with obesity. We aimed to analyze miR-21 expression levels in relation to diabetes and obesity to determine the effect that miR-21 mimic has on processes involved in WAT functionality, to dissect the underlying molecular mechanisms, and to study the potential therapeutic application of the miR-21 mimic against obesity. We found higher miR-21 levels in WAT from non-diabetic obese compared to normoweight humans and mice. Moreover, in 3T3-L1 adipocytes, miR-21 mimic affect genes involved in WAT functionality regulation and significantly increase the expression of genes involved in browning and thermogenesis. Interestingly, in vivo treatment with the miR-21 mimic blocked weight gain induced by a high-fat diet in obese mice, without modifying food intake or physical activity. This was associated with metabolic enhancement, WAT browning, and brown adipose tissue (AT) thermogenic programming through vascular endothelial growth factor A (VEGF-A), p53, and transforming growth factor β1 (TGF-β1) signaling pathways. Our findings suggest that miR-21 mimic-based therapy may provide a new opportunity to therapeutically manage obesity and consequently, its associated alterations., Competing Interests: The authors have no competing interests., (© 2021 The Author(s).)

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB 1 R) and type 2 (CB 2 R). Herein, we synthesized the (+)-enantiomer of CBD and its derivative (+)-CBD hydroxypentylester ((+)-CBD-HPE) that showed enhanced CB 1 R and CB 2 R binding and functional activities compared to their respective (-) enantiomers. (+)-CBD-HPE Ki values for CB 1 R and CB 2 R were 3.1 ± 1.1 and 0.8 ± 0.1 nM respectively acting as CB 1 R antagonist and CB 2 R agonist. We further tested the capacity of (+)-CBD-HPE to prevent hyperglycemia and its complications in a mouse model. (+)-CBD-HPE significantly reduced streptozotocin (STZ)-induced hyperglycemia and glucose intolerance by preserving pancreatic beta cell mass. (+)-CBD-HPE significantly reduced activation of NF-κB by phosphorylation by 15% compared to STZ-vehicle mice, and CD3 + T cell infiltration into the islets was avoided. Consequently, (+)-CBD-HPE prevented STZ-induced apoptosis in islets. STZ induced inflammation and kidney damage, visualized by a significant increase in plasma proinflammatory cytokines, creatinine, and BUN. Treatment with (+)-CBD-HPE significantly reduced 2.5-fold plasma IFN-γ and increased 3-fold IL-5 levels compared to STZ-treated mice, without altering IL-18. (+)-CBD-HPE also significantly reduced creatinine and BUN levels to those comparable to healthy controls. At the macroscopy level, (+)-CBD-HPE prevented STZ-induced lesions in the kidney and voided renal fibrosis and CD3 + T cell infiltration. Thus, (+)-enantiomers of CBD, particularly (+)-CBD-HPE, have a promising potential due to their pharmacological profile and synthesis, potentially to be used for metabolic and immune-related disorders., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce reactive astrogliosis in an attempt to preserve the neuronal network and re-establish glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote reactive astrogliosis and increase susceptibility of neurons to stress-induced apoptosis. Such effects could be reversed by ORY1001 treatment both in vitro and in vivo , paving the way for a new therapeutic approach for Type 2 Diabetes Mellitus., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The genus Amblyomma is the most representative tick genus in Brazil and some species act as vectors of pathogenic organisms to animals and humans. Information on the seasonal dynamics of Amblyomma spp. as well as on rickettsial organisms infecting these ticks in some regions in Brazil is still fragmentary. Herein, we investigated the seasonal dynamics and rickettsial infections in Amblyomma dubitatum ticks collected in the Atlantic forest biome in north-eastern Brazil. Using carbon dioxide traps, ticks were collected monthly for two consecutive years. In total, 15,789 ticks were collected: 69 females (0.4%), 116 males (0.7%), 1,067 nymphs (6.8%), and 14,537 larvae (92.1%). All nymphs, females and males were identified as A. dubitatum, whereas larvae were identified as Amblyomma spp. Larvae were more frequent in summer (77% of the larvae collected), whereas nymphs were collected with similar frequency in summer (32.8%), autumn (30.0%) and spring (28.4%). Adults were more frequent in spring (47.6%). A total of 648 ticks (485 nymphs, 60 females, and 103 males) were tested by PCR for the gltA gene of Rickettsia spp. and 87 (13.4%; 95% CI: 10.9-16.3%) were positive. A consensus sequence (size, 350 bp) of 66 gltA gene sequences indicate that the organism detected herein is similar to Rickettsia tamurae, Rickettsia monacencis and Rickettsia sp. strain Pampulha. One of these positive samples was also positive for the ompA gene of spotted fever group rickettsiae, but attempts to sequence the amplicon were not successful. We also tested this sample by a PCR targeting the rickettsial htrA gene, but no amplification product could be detected. This study indicates that A. dubitatum may be a common tick in areas where capybaras are present in north-eastern Brazil, occurring during the whole year. It also suggests the circulation of a spotted fever group rickettsia in this A. dubitatum population, whose identity has yet to be determined., (Copyright © 2021. Published by Elsevier B.V.)